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Interpretive Handbook

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Test 86208 :
15q Deletion, Type I and Type II Characterization, Prader-Willi/Angelman Syndromes, FISH

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Prader-Willi (PWS) and Angelman (AS) syndromes are 2 distinct syndromes that can result from either a paternal or maternal deletion of 15q11-q13, respectively. Other mechanisms of inheritance include maternal uniparental disomy (UPD) in PWS, paternal UPD in AS, or abnormal methylation and gene expression.

 

Both type I and type II 15q11-q13 deletions have been described. Type 1 deletions are larger deletions, spanning breakpoint (BP)1 and distal BP3 breakpoints, while type II deletions are smaller (approximately 500kb), spanning BP2 and BP3. Depending on the deletion type, behavioral differences have been reported in both PWS and AS patients. Type I patients have more severe phenotypes including delayed development and autistic features. Distinguishing between type I and type II deletions is useful in counseling PWS or AS patients. Type I and II deletions may be detected by evaluating the RP11-289D12 region on chromosome 15 with specific DNA probes.

 

A +dic(15) marker chromosome (an extra or supernumerary dicentric chromosome 15) is often familial and is usually consistent with a normal phenotype, but depending on its size, the marker can be associated with PWS or AS. Larger dic(15) are usually new mutations and are associated with mental retardation and mild dysmorphic features.

 

See Prader-Willi and Angelman Syndromes: Laboratory Approach to Diagnosis in Special Instructions for additional information.

Useful For Suggests clinical disorders or settings where the test may be helpful

Differentiating between type I and type II deletions in Prader-Willi syndrome and Angelman syndrome patients, as follow-up testing after a SNRPN or D15S10 deletion has been detected by FISH analysis or in patients with a +dic(15) chromosome lacking the SNRPN or D15S10 loci (see DUP15 / 15q11.2 Duplication, FISH)

 

Mapping duplications in patients who carry a +dic(15) marker chromosome

Interpretation Provides information to assist in interpretation of the test results

Any individual with a normal signal pattern (2 signals) in each metaphase is considered negative for a deletion in the region tested by this probe (see Cautions).

 

Any patient with a FISH signal pattern indicating loss of the critical region will be reported as having a deletion of the region tested by this probe.

 

This test should be performed as a reflex test when a SNRPN or D15S10 deletion has been detected by FISH analysis or in patients with a dic(15) chromosome lacking the SNRPN or D15S10 loci.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Because this FISH test is not approved by the FDA, it is important to confirm Prader-Willi syndrome (PWS) or Angelman syndrome (AS) diagnoses by other established methods, such as medical history and clinical evaluation.

 

This test does not detect uniparental disomy or other methylation abnormalities that cause the PWS or AS phenotype.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Butler MG, Bittel DC, Kibiryeva N, et al: Behavioral differences among subjects with Prader-Willi syndrome and type I and type II deletion and maternal disomy. Pediatrics 2004 Mar;113(3 pt 1):565-573

2. Varela MC, Kok F, Setian N, et al: Impact of molecular mechanisms, including deletion size, on Prader-Willi syndrome phenotype: study of 75 patients. Clin Genet 2005 Jan;67(1):45-52

3. Chai JH, Locke DP, Greally JM, et al: Identification of four highly conserved genes between breakpoint hotspots BP1 and BP2 of the Prader-Willi/Angelman syndromes deletion region that have undergone evolutionary transposition mediated by flanking duplicons. Am J Hum Genet 2003 Oct;73(4):898-925